Over-expression of two copies (but not one) of Hsap\GFAPScer\UAS.cWa driven in glia by Scer\GAL4repo.PU leads to Rosenthal fiber-like inclusion formations in 20 day old flies.
Expression of Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo does not affect developmental rate or eclosion. Overall brain structure appears normal at 1 day of age, as assayed by haematoxylin and eosin. A TUNEL assay for apoptotic cells does not reveal dying cells at 1 day after eclosion. However, increasing numbers of TUNEL-positive cells are seen as the animals age, indicating some limited toxicity. The TUNEL-positive cells are widespread, with no obvious predilection for particular areas of the brain. In the lamina, there is a trend towards decreased numbers of glial cells with advancing age and a significant loss of neurons at 10 and 20 days of age, consistent with a non-autonomous effect.
Expression of Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo promotes the loss of GluRIIB-expressing neurons which is particularly apparent by 20 days after eclosion.
Flies expressing Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo exhibit a significantly increased frequency of seizures in response to mechanical stimulation.
Flies expressing Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo display some abnormal protein aggregation (although less than in Hsap\GFAPR79H.Scer\UAS mutants), with numerous eosinophilic, elongated and beaded inclusions. The number of inclusions increases with age.
Flies expressing Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo display an increase in autophagy induction with age, with a modest induction present at 1 day after eclosion and more substantial induction at 10 and 20 days of age.
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, enhanceable by Catn1/Cat[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, enhanceable by Catn1/Cat[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, enhanceable by Sod1n1/Sod[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, enhanceable by Sod1n1/Sod[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, suppressible by l(2)eflUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, suppressible by l(2)eflUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, suppressible by Hsp26UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, suppressible by Hsp26UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, suppressible by Hsp27UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, suppressible by Hsp27UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, suppressible by CatUAS.cAa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, suppressible by CatUAS.cAa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, suppressible by Hsap\HSPA1AUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, suppressible by Hsap\HSPA1AUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, suppressible by Hsap\SOD1UAS.cWb, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, suppressible by Hsap\SOD1UAS.cWb, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has increased cell death | progressive phenotype, suppressible by Eaat1UAS.cRa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has paralytic phenotype, suppressible by Eaat1UAS.cRa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, enhanceable by Catn1/Cat[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, enhanceable by Catn1/Cat[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, enhanceable by Catn1/Cat[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, enhanceable by Sod1n1/Sod[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, enhanceable by Sod1n1/Sod[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, enhanceable by Sod1n1/Sod[+]
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, suppressible by l(2)eflUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, suppressible by l(2)eflUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, suppressible by CatUAS.cAa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, suppressible by CatUAS.cAa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, suppressible by Hsap\HSPA1AUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, suppressible by Hsap\HSPA1AUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, suppressible by Hsap\HSPA1AUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, suppressible by Hsap\SOD1UAS.cWb, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, suppressible by Hsap\SOD1UAS.cWb, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, suppressible by Hsap\SOD1UAS.cWb, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, suppressible by Eaat1UAS.cRa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, suppressible by Eaat1UAS.cRa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, suppressible by l(2)eflUAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, suppressible by Eaat1UAS.cRa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, suppressible by Hsp26UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, suppressible by Hsp26UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, suppressible by Hsp26UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, suppressible by Hsp27UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, suppressible by Hsp27UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has neuron | cell non-autonomous phenotype, suppressible by Hsp27UAS.cWa, Scer\GAL4repo
Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, suppressible by CatUAS.cAa, Scer\GAL4repo
Overexpression of l(2)eflScer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of l(2)eflScer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies and in activation of autophagy.
Overexpression of Hsp26Scer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsp26Scer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies.
Overexpression of Hsp27Scer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsp27Scer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies.
Overexpression of CatScer\UAS.cAa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of CatScer\UAS.cAa also decreases the number of seizures. Protection from cellular toxicity does not alter the number of inclusion bodies.
A Catn1 heterozygous background significantly enhances Hsap\GFAPScer\UAS.cWa toxicity and increases the frequency of mechanically-stimulated seizures in these flies. An increase in cellular toxicity does not alter the number of inclusion bodies but does increase autophagy induction.
A Sodn1 heterozygous background significantly enhances Hsap\GFAPScer\UAS.cWa toxicity and increases the frequency of mechanically-stimulated seizures in these flies. Protection from cellular toxicity does not alter the number of inclusion bodies. An increase in cellular toxicity does not alter the number of inclusion bodies but does increase autophagy induction.
Overexpression of Hsap\HSPA1AScer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsap\HSPA1AScer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies and in activation of autophagy.
Overexpression of Hsap\SOD1Scer\UAS.cWb in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsap\SOD1Scer\UAS.cWb also decreases the number of seizures. Protection from cellular toxicity does not alter the number of inclusion bodies.
Expression of Eaat1Scer\UAS.cRa significantly suppresses the Hsap\GFAP toxicity, but does not influence inclusion formation, Hsap\GFAP solubility or autophagy induction.